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Conclusion This review provides very limited support for the use of antipyretics in preventing febrile seizure recurrence within the same fever episode and no evidence for its use in distant fever episodes. New studies are required to evaluate this topic further and determine whether the effectiveness of antipyretics is based on intervention timing. What is Known • Reviews of prophylactic drug management among febrile seizure children found that antipyretics had no significant benefits. • Recent data suggest that antipyretics are effective in preventing febrile seizures. What is New • Weak evidence suggests a possible role in preventing febrile seizure recurrence within the same fever episode. • There is clearly no role for antipyretic prophylaxis in preventing febrile seizures during distant fever episodes. Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT). Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 μg of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1α, IL-6, TNFα, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy. PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15. We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT. Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy. Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy. We aimed to investigate the efficacy of flumazenil infusion in the maintenance of arousal and prevention of development of complications in severe benzodiazepine poisoning. Sixty severely poisoned patients (intubated due to loss of consciousness) intoxicated by sole benzodiazepines referred to Loghman Hakim hospital between May 2018 and August 2019 were considered to be included in the current study. All were evaluated for possible contraindications of flumazenil administration. If there were no contraindications, we continued supportive care in one group and supportive care plus flumazenil infusion in the second group. Following response to the stat dose of flumazenil, complications, hospital stay, and outcome were compared between these two groups. A total of 60 benzodiazepine-poisoned patients aged between 16 and 84 years old (37 males and 23 females) were enrolled. There was no statistically significant difference between these two groups regarding the period of hospital stay. Need for intubation significantly decreased in the infusion group. None of the patients experienced seizure or dysrhythmia. One patient died in the control group which received only a stat dose of flumazenil. Administration of flumazenil is safe in benzodiazepine-poisoned patients with appropriate indications. Flumazenil infusion can significantly decrease the need for intubation and subsequent ICU admission. Even though flumazenil is an expensive antidote, its administration may decrease the need for ICU beds in the setting of acute poisoning. Administration of flumazenil is safe in benzodiazepine-poisoned patients with appropriate indications. Flumazenil infusion can significantly decrease the need for intubation and subsequent ICU admission. Even though flumazenil is an expensive antidote, its administration may decrease the need for ICU beds in the setting of acute poisoning. To characterize the safety, pharmacodynamics, and pharmacokinetics (PK) of vericiguat in healthy males. Six phase I studies were conducted in European, Chinese, and Japanese males. Subjects received oral vericiguat as a single dose (0.5-15.0mg solution [for first-in-human study] or 1.25-10.0mg immediate release [IR tablets]) or multiple doses (1.25-10.0mg IR tablets once daily [QD] or 5.0mg IR tablets twice daily for 7 consecutive days). Bioavailability and food effects on vericiguat PK (IR tablets) were also studied in European subjects. Overall, 255 of 265 randomized subjects completed their respective studies. There were no deaths or serious adverse events. Vericiguat was generally well tolerated at doses ≤ 10.0mg. In the first-in-human study, the most frequent drug-related adverse events were headache and postural dizziness (experienced by five subjects each [7.2%]). Three of four subjects who received vericiguat 15.0mg (oral solution, fasted) experienced orthostatic reactions. Vericiguat (≤ 10.0mg, IR tablets) was rapidly absorbed (median time to reach maximum plasma concentration ≤ 2.5h [fasted]) with a mean half-life of about 22.0h (range 17.9-27.0h for single and multiple doses). No evidence for deviation from dose proportionality or unexpected accumulation was observed. Administration of vericiguat 5.0mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval] 108; 131]), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state. In general, vericiguat was well tolerated. https://www.selleckchem.com/ These results supported further clinical evaluation of vericiguat QD in patients with heart failure. EudraCT 2011-001627-21; EudraCT 2012-000953-30. EudraCT 2011-001627-21; EudraCT 2012-000953-30.
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